Apparatus for characterizing particles and method for use in characterizing particles

ABSTRACT

A particle characterization apparatus is disclosed comprising: a first light source; a second light source, a sample cell; a first detector and a second detector. The first light source is operable to illuminate a first region of a sample comprising dispersed particles within the sample cell with a first light beam along a first light beam axis so as to produce scattered light by interactions of the first light beam with the sample. The first detector is configured to detect the scattered light. The second light source is operable to illuminate a second region of the sample with a second light beam along a second light beam axis. The second detector is an imaging detector, configured to image the particles along an imaging axis using the second light beam. The first light beam axis is at an angle of at least 5 degrees to the second light beam axis.

CROSS REFERENCE TO RELATED APPLICATION APPLICATIONS

This application is a U.S. Non-Provisional patent application claimingreissue application of U.S. Pat. No. 9,897,525 B2 which issued from U.S.patent application Ser. No. 15/139,128, filed Apr. 26, 2016, whichclaims priority to European Patent Application No. EP15166133, filed May1, 2015, and is hereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates to an apparatus for characterisingparticles, and to a method for use in characterising particles.Characterising particles may comprise determining a distribution ofparticle size.

BACKGROUND

It is known that particles in a sample can be characterised byilluminating the sample and measuring the light scattered by theparticles. The particles of the sample are typically dispersed within asample cell in a dispersant medium during measuring. The dispersantmedium is typically air or water, and typically flows through the samplecell during measurement.

The correlation between light scattering and particle characteristicscan be described by the well-known Mie solution to Maxwell's equations.Smaller particles tend to result in larger scattering angles, and largerparticles result in smaller scattering angles. The light scattered ateach of a range of angles from the sample can be used to determine, forexample, a size distribution of the particles in the sample. Such ameasurement may be referred to as a light (e.g. laser) diffractionparticle characterisation.

Much of the development of instruments for light diffraction particlecharacterisation has been directed towards increasing the size range ofparticles that can be characterised at one time. At the same time, thereis a demand to reduce the size of the instrument. The requirements for agreater measurement range and a smaller instrument are in conflict,which may result in technical difficulties in achieving sufficientperformance, or a reduced quality of measurement. In particular, thetechnical requirements for achieving accurate characterisation of largerparticles are particularly challenging and expensive. There may be adiscrepancy between the cost of the components needed to achieve largeparticle characterisation and the perceived value associated with thesemeasurements.

An instrument for characterisation of particles by light diffractiontypically works by measuring the intensity of light scattered by fineparticles suspended in a strong monochromatic light source of knownintensity. The instrument needs to measure the intensity of light at aseries of angles measured from the illumination direction, becausedifferent sizes of particles scatter light at different angles.Generally a large particle will scatter light at an angle very close tothe axis of the illuminating beam, and a smaller particle will scatterlight at a larger angle. Because the illuminating beam is much strongerthan the scattered light a detector is typically used that allows lightto pass through without touching the detector. Otherwise, theillumination beam incident on the detector would produce a very largereflection that can leak into neighbouring detectors. The reflectedlight would tend to bounce all around the inside of the instrument,overwhelming the much smaller scattered light signals.

Larger particles scatter light at angles close to the axis of theillumination beam (e.g. a laser). To separate the scattered light fromthe illumination light it is necessary either to measure with detectorsclose to the focused spot of the illumination beam, or to use a longerfocal length in order to allow the illumination beam and scattered lightto separate out. The former approach means that the detector andillumination beam must be very accurately aligned, and the secondapproach results in a very long instrument that may have stabilityproblems.

As particle size becomes smaller, the useful scattered light changes intwo ways. The peak intensity is scattered at a larger angle to theillumination beam axis and the scattering becomes more isotropic. A sizeof particle will eventually be reached where the scattered light isalmost completely isotropic, and therefore the instrument cannot tellthe difference between particles at this size and particles that aresmaller. This sets the lower size limit for a light diffractioninstrument. However, because the particle size at which the scatteringbecomes isotropic depends on the wavelength of the light, it is possibleto extend the bottom size limit for an instrument by changing to ashorter wavelength light source.

One approach is to use a red Helium Neon laser at 633 nm to measure thelargest particles and a blue non-coherent light source (such as an LEDor filtered incandescent lamp) to allow measurement of the fineparticles. A large component of the cost of such an instrument isassociated with the components needed to measure the large particles:the laser must have a very high beam quality, and the detector must bepositioned to almost sub-micron tolerances.

One solution might be to limit the maximum particle size that may becharacterised by the instrument, but even when measuring fine particlesit is often desirable to be confident that there are no large particlespresent. Any system that limits the top size too far may also limit theability to report problems with aggregates and contaminants.

A solution that addresses or ameliorates at least some of the abovementioned problems is desired.

BRIEF SUMMARY OF THE INVENTION

According to the present invention, there is provided a particlecharacterisation apparatus comprising: a first light source; a secondlight source, a sample cell; a first detector and a second detector;wherein:

the first light source is operable to illuminate a first region of asample comprising dispersed particles within the sample cell with afirst light beam along a first light beam axis so as to producescattered light by interactions of the first light beam with the sample;

the first detector is configured to detect the scattered light;

the second light source is operable to illuminate a second region of thesample with a second light beam along a second light beam axis;

the second detector is an imaging detector, configured to image theparticles along an imaging axis using the second light beam; and

the first light beam axis is at an angle of at least 5 degrees to thesecond light beam axis.

The first light beam axis may be at an angle of at least: 10, 15, 20, 25or 30 degrees to the second light beam axis.

The imaging axis may be at an angle of at least: 5, 10, 15, 20, 25, or30 degrees from the first light beam axis.

The sample cell may comprise a first wall and a second wall. The firstlight beam may pass through the first wall, then through the sample,then through the second wall. The first and second wall of the samplecell may each comprise a convex external surface through which the firstlight beam axis and the second light beam axis passes.

The first and second wall may each comprise a plano-convex lens definedby the respective convex external surface, the optical axes of the firstand second wall defining a sample cell optical axis.

The second light beam axis may be at an angle of at least 10° to thesample cell optical axis.

The first light source, sample cell and first detector may define ascattering plane, and the second light source and second detector may bedisposed offset from the scattering plane, occupying a differentazimuthal orientation about the first light beam axis.

The first light source may be coherent. The second light source may beincoherent.

The second detector may comprise a two dimensional array of lightsensitive elements.

The first detector may comprise an array of detector elements, arrangedto detect light scattered at a range of scattering angles.

The first light source may have a wavelength of less than 550 nm. Thefirst light source may have a wavelength of less than 500 nm, 450 nm or400 nm.

The particle characterisation apparatus may comprise an imaging lensbetween the second detector and the sample cell. The imaging lens maycomprise an entocentric lens.

The particle characterisation apparatus may further comprise acollecting lens between the sample cell and the first detector. Thecollecting lens may comprise an aspheric surface.

The collecting lens may comprise an optical axis that is coincident withthe first light beam axis.

The processor may be configured to correct a size of an imaged particlebased on a location of the particle image at the second detector.

The particle characterisation apparatus may further comprise a condenserlens between the second light source and the sample cell. A collectorlens may be provided between the condenser lens and the second lightsource. The second light source, collector lens and condenser lens maybe arranged to provide Köhler illumination of a region within the samplecell.

The second detector may be arranged on a path of the second light beam,so as to perform light field imaging of particles within the samplecell.

The second detector may be arranged off the path of the second lightbeam, so as to perform dark field imaging of particles within the samplecell.

The particle characterisation apparatus may comprise a third lightsource arranged to provide a third light beam that is not directlyreceived by the second detector, so that the apparatus is configured toperform dark field imaging when the sample is illuminated by the thirdlight source and not by the second light source.

The particle characterisation apparatus may further comprise a lighttrap behind a sample cell region that is imaged by the second detector.

The light trap may be provided around the second light source, forproviding a dark field background when the sample is illuminated by thethird light source.

The apparatus may be configured to perform a static light scatteringmeasurement to derive a particle size from an output of the firstdetector. The apparatus may be configured to perform a dynamic lightscattering measurement from an output of the first detector.

The first region may be at least partly coincident with the secondregion.

The apparatus may comprise a processor, configured to correlate orcross-reference data from the first detector with data from the seconddetector (or vice-versa). The output from the second detector may beused to improve a measurement derived from the first detector (and viceversa). This may be particularly applicable where the first (scatteringdetection) region is at least partly co-incident with the second(imaging detection) region.

The output from the second detector may be used to identify or confirmparticle aggregation or breakup, check the uniformity of mixing, andgate data from the first sensor when the sample appears atypical. Thesecond detector may identify particles that are too large to be measuredby the first detector. While such particles are within the firstillumination beam, the output of the first detector may be ignored ordiscarded. This may improve the fidelity of a measurement.

Where the second detector identifies that particles of a specific sizerange are present in the sample, a mathematical model used to relate thescattered light measured at the first detector to a particle sizedistribution may be constrained to include particles of this size range.This may improve the speed and reliability with which measurements fromthe first detector can be related to particle characteristics.

Embodiments of the invention will now be described, purely by way ofexample, with reference to the accompanying drawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is described in further detail below by way of examplesand with reference to the accompanying drawings, in which:

FIG. 1 is a schematic diagram of an instrument in which an imagingdetector with light field illumination is combined with a scatteringdetector;

FIG. 2 is a schematic diagram of an instrument in which a scattering(first) detector is combined with an imaging (second) detector, withdark field illumination;

FIG. 3 is a schematic diagram of an instrument in which an imagingdetector with both dark field and light field illumination is combinedwith a scattering detector;

FIG. 4 is a ray diagram of an instrument with a back-scattered lightdetector, a forward-scattered light detector, and imaging detector withlight field illumination;

FIG. 5 is a ray diagram of a further example of an instrument with aback-scattered light detector, a forward-scattered light detector, andan imaging detector with light field illumination;

FIG. 6 is a ray diagram of an optical arrangement for an imagingdetector and associated focussing optics for a lensed sample cellincluding the second wall of the sample cell;

FIG. 7 is a ray diagram of a an optical arrangement for an imagingdetector and associated focussing optics for a flat sample cell,including the second wall of the sample cell; and

FIG. 8 is a ray diagram of an optical arrangement for an imagingdetector and associated focussing optics for a lensed sample cellincluding the second wall of the sample cell, in which the focussingoptics comprise a field correction lens between the imaging detector andthe main focussing optical group.

DETAILED DESCRIPTION

A number of arrangements are possible for a hybrid instrument that bothimages particles and detects scattered light from particles.

One approach is to use the light source for light scattering (which isusually a laser) as a light source. The imaging detector can be placedon the opposite side of the sample cell to the light source, whichresults in a bright field illumination, with the particles appearing asdark shapes against a bright background. This approach has a number ofdisadvantages. A laser light source typically has a Gaussian intensityprofile, which means that particles at the edge of the light beam areless brightly illuminated than particles in the centre of the lightbeam. Furthermore, because of the coherency of the light, the edges ofdark particles will be blurred by diffraction rings. In addition, thelaser cannot be allowed to clip edges of the sample cell, or stray lightwill be scattered as diffraction lines. This means that there must be adark area at either side of the sample cell with no illumination, whichmeans that some particles cannot be imaged.

Another approach is to use a different light source for imagingillumination, with beam splitters and dichroic mirrors to allow theimaging illumination and imaging detector to image through the lightscattering illumination axis. A quarter wave plate (and perhaps apolariser) may be needed to eliminate back-reflection from the imagingdetector focal plane array, which may interfere with any back-scatteringmeasurements. If the dichroic mirrors are left in place, strayreflections may be caused that could distort the backscattermeasurements.

A further approach is to use an first and second sample cell connectedin series, and perform light scattering measurements on the sample as itpasses through the first cell, and particle imaging as the sample passesthrough the second cell. A drawback with this approach is that there isa time lag between the scattering and imaging measurements on the sameportion of a flowing sample, making it difficult to successfullycorrelate the different types of measurement. Combined measurements oftime dependent particle phenomena, such as crystallisation andaggregation, are not possible with such an arrangement.

Furthermore, the use of a first and second sample cell in a flow circuitwill increase pressure drop along a fluid circuit comprising the firstand second sample cell. Increased pump pressure would therefore beneeded. The increased pump power and pressure associated with such anarrangement is more likely to alter fragile particles and emulsions. Inaddition, adding a further sample cell adds a great deal of extra cost.The cost of an imaging sample cell would be similar to the cost of ascattering sample cell, as it would be performing a similar function.

A separate second flow cell (for imaging) also may make a fluid pathcomprising the first and second flow cell more difficult to fill, drainand clean. If the second (imaging) flow cell were placed at the sameheight as the first (scattering) cell, then there would be areas in thepiping between the two cells that would form u-bend sumps, and would notdrain properly. In addition there would be upper loops of piping thatmay form air traps. Bubbles could be shed at any time to contaminatemeasurements, and the fluid path would be restricted. If the imagingsample cell were placed at a different height (e.g. above or below thescattering sample cell), the combined instrument would be much taller.Although such a system might drain adequately, it would be difficult tofill, due to the increased pump head needed to prime the system andclear air out of the pipes.

Referring to FIG. 1 , an instrument is shown, comprising first lightsource 101, second light source 102, sample cell 105, first detector111, second detector 112 and illumination lens 108.

The sample cell 105 comprises a sample 150, held between a first andsecond cell wall 141, 142. In this example the interior and exteriorsurfaces of each cell wall are flat and parallel, but in otherembodiments this may not be so. The sample 150 comprises particlesdispersed in a fluid, such as water.

The first light source 101, illumination lens 108 and first detector 111are configured to perform a static light scattering measurement. Thefirst light source 101 is configured to illuminate a first region of thesample 150 within the sample cell 105 by producing a first light beam121 along a first light beam axis 131. The first light beam 121 andfirst light beam axis 131 pass through the illumination lens 108, thenthrough the first wall 141 of the sample cell 105, through the sample150 and through the second wall 142 of the sample cell 105. The firstlight beam 121 may be focussed near the first detector 111, butpreferably does not illuminate the first detector 111. The firstdetector 111 may, for instance, include a hole through which the firstlight beam 121 passes. The first light beam 121 may be received in alight trap (not shown). The light trap may include light measuring means(not shown) for measuring the power of the first light beam 121.

The first light source 101 may comprise a coherent light source, forexample having a wavelength of less than 550 nm. For example the firstlight source 101 may comprise a blue or violet laser. The first lightsource 101 may comprise a laser diode.

The illumination lens 108 produces a first light beam 121 thatilluminates the first region of the sample. The first light beam 121 mayconverge through the sample, be collimated in the sample, or may divergein the sample.

The first detector 111 is configured to detect light scattered byinteractions of the first light beam 121 with the particles of thesample 150 in the first region (which may be referred to as a scatteringregion). The first detector 111 may comprise a plurality (e.g. an array)of detector elements each corresponding with a different range ofscattering angles. The detector elements may each comprise photodiodes(for example, formed on a silicon substrate). The first detector 111 mayfor instance, comprise a one dimensional array of detector elements.Each detector element may be annular, with the centre of each annulussubstantially coincident with the first light beam axis 131.Alternatively, each detector element may be arc shaped, with the centreof each arc co-incident with the first light beam axis 131.

In this example, the first detector 111 is arranged to detect forwardscattered light. Forward-scattered light may be defined as light that isscattered in a direction that is at less than or equal to 90 degreesfrom the direction of the first light beam axis 131, with back-scatteredlight being defined as light that is scattered in a direction that ismore than 90 degrees from the direction of the first light beam axis131.

The second light source 102 produces a second light beam 122 along asecond light beam axis 132. The second light beam 122 illuminates asecond region of the sample cell 105 that overlaps with the firstregion. The second region may comprise (or contain) the first region.The second light source 102 is preferably configured to providesubstantially uniform illumination of the second region. The secondregion may encompass the breadth of the sample cell 105 (lateral to aflow direction through the sample cell 105).

The second light source 102 may comprise a non-coherent light source,such as an LED, incandescent lamp, or any other light source. The secondlight source 102 may be broad band (i.e. comprising more than onewavelength of light), or may be monochromatic.

The second detector 112 is an imaging detector (such as a camera), andis configured to image particles within the second region along animaging axis. The imaging axis in this embodiment is coincident with thesecond light beam axis 132. The second detector 112 may be arranged toimage a third region of the sample 150 (which may be referred to as animaging region), so that measurements from the first detector 111 andsecond detector 112 may be compared and correlated (for example, as afunction of time). The imaging region may be arranged to besubstantially coincident with, or a subset of, the scattering region. Animaging lens (not shown) may be provided for focussing light from theimaging region onto a focal plane of the second detector 112.

For example, the output from the first detector 111 may be used todetermine a first particle size distribution. For example, the firstdetector 111 may be arranged to detect diffracted light from theparticles, and the instrument may be configured to perform a lightdiffraction measurement (e.g. static light scattering) by processing theoutput of the first detector to determine a first particle sizedistribution based on Mie theory (or the Fraunhofer approximation).

The instrument may be configured to determine a second particle sizedistribution, using the output from the second detector. The secondparticle size distribution may be determined by processing images ofparticles. A first range of particle size that may be characterisedusing data from the second detector will be constrained by at least oneof the diffraction limit of the optics, the wavelength of the secondlight source and the spatial resolution of the second detector. Asalready discussed, a second range of particle sizes that cancharacterised by a light diffraction measurement is also constrained (atthe upper limit by path length and minimum scattering detection angle).The instrument may be configured such that the first range of particlesize partially overlaps with the second range of particle size.

Parameters for adjusting the first particle size distribution may bedetermined from comparing the second particle size distribution with thefirst particle size distribution. For example, the first particle sizedistribution may be adjusted to match the second particle sizedistribution in the region of overlap between the first and second rangeof particle size.

In some embodiments the instrument may also be configured to determineparticle shape parameters using the data from the second detector. Theparticle shape parameters may be used to adjust the first particle sizedistribution. For example, Mie scattering theory is based on theassumption that particles are spherical. Where the particle shapeparameters indicate that the particles are not generally spherical, acorrection may be applied to the first particle size distribution toaccount for this. The correction may be selected to make the firstparticle size distribution match the second particle size distributionin the region of overlap.

In some embodiments, the second particle size distribution may be usedto calibrate the first particle size distribution in the region ofoverlap. The first particle size distribution may alternatively be usedto calibrate the second particle size distribution in the region ofoverlap.

The first and second particle size distributions may be combinedtogether to form a single common distribution over the combined firstand second range of particle size.

The first light source 101 and second light source 102 may be configuredto be rapidly switched on and off, to alternate illumination of thesample 150 by the first and second light beam 121, 122 respectively. Theperiod of switching may be less than: 10 seconds, 5 seconds, 1 second,500 ms, 250 ms, 100 ms, or 50 ms. Such an approach eliminates any straylight contamination of a scattering measurement with the second lightbeam, and of the imaging measurement by the first light beam.Alternatively, the first light source 101 and second light source 102may be configured to illuminate the sample 150 at the same time, toallow simultaneous measurement by scattering and imaging.

An instrument in which the first light beam axis 131 is at an angle tothe second light beam axis 132 can be arranged so that none of theimaging components lie on scattering planes, defined by the sample celland the elements of the first detector 111. This greatly reduces thechance of stray reflections distorting scattering measurements.Backscatter measurements (for very small particles) may therefore bewithout contamination from the second light source. In addition,following this approach an instrument may be produced that does notinclude at least one of: beam splitters, mirrors, polarisers, quarterwave plates or other moving elements for switching between modes(scattering and imaging). An instrument can thereby be produced that isboth low cost and reliable.

In some embodiments, a requirement for the scattering measurementarrangement (comprising the first light source 101 and first detector111) to characterise larger particles (for instance, larger than 100 μm)may be relaxed, and the imaging measurement arrangement (comprising thesecond light source 102 and second detector 112) may be relied on tocharacterise these larger particles. In such an arrangement, thescattering measurement arrangement may be made relatively low cost, byusing a single, short wavelength light source (for example below 550nm), such as a blue or violet laser diode.

An instrument with a single wavelength first light source 101 (for thescattering measurement arrangement) can use a more simpleanti-reflective (AR) coating on optical elements associated with thescattering measurement arrangement. Such single wavelength AR coatingshave reduced cost and are simpler to produce.

Since the sample cell 105 is relatively thin, an entocentric lens may beused to image particles on the second detector (rather than atelecentric lens).

The inclination of the imaging axis relative to the sample cell 105means that the distance from the focal plane of the second detector 112is not uniform across the imaging region of the sample 150. Particles atthe top of the sample cell 105 (as shown in FIG. 1 ) will be furtheraway from the second detector 112 than particles at the bottom of thesample cell 105. This may cause the particles in different positionswithin the imaging region to have different magnification at the focalplane. The instrument may be configured to compensate for suchmagnification (e.g. using a processor), based on the position of theimaged particle on the second detector 112.

Referring to FIG. 2 , an alternative instrument is shown, comprisingfirst light source 101, second light source 102, third light source 103,sample cell 105, first detector 111, second detector 112, illuminationlens 108 and light trap 160.

In this arrangement the scattering measurement arrangement may includeany of the features described with reference to FIG. 1 .

The second light source 102 in this instrument also produces a secondlight beam 122 along a second light beam axis 132. The second light beam122 illuminates a second region of the sample cell 105 that overlapswith the first region (illuminated by the first light beam 121, asdescribed with reference to FIG. 1 ). The second region may comprise (orcontain) the first region. The second light source 102 is preferablyconfigured to provide substantially uniform illumination of the secondregion. The second region may encompass the breadth of the sample cell105 (lateral to a flow direction through the sample cell 105).

Although these features are in common with the arrangement of FIG. 1 ,in the arrangement of FIG. 2 the second light beam axis is notcoincident with (or parallel to) the imaging axis 135. Instead there isan angle between the second light beam axis and the imaging axis 135,which may be at least 15 degrees. The angle between the second lightbeam axis and the imaging axis 135 is selected such that the seconddetector 112 does not receive light directly from the second lightsource 102. Instead, the second detector 112 is arranged to receive onlylight from the second light beam 122 that has interacted with particlesof the sample, for instance by reflection or refraction. Such reflectionwill result in a highlight line at the edge of each particle, imaged ona dark field (i.e. a dark background image).

Dark field imaging may be more appropriate for particles that aretranslucent or completely transparent, which may be less visible in alight field imaging arrangement.

A third light source 103 may be provided, producing a third light beam123 along a third light beam axis. The third light beam 123 illuminatesat least part of the second region of the sample cell 105. The thirdlight beam axis is at a different (non-zero) angle to the imaging axis135. The angle between the third light beam axis and the imaging axis135 is selected such that the second detector 112 does not receive lightdirectly from the third light source 103. The third light source 103 isarranged to highlight edges of particles from a different direction.

The light trap 160 may be arranged to improve the contrast between thebright particle images and the dark field background, by trapping straylight behind the sample cell 105 along the imaging axis 135. The lighttrap 160 is thereby configured to provide a dark(er) background to theimaged particles.

Further dark field light sources may be provided (not shown), similar tothe second and third light source 102, 103, to provide further darkfield illumination of the sample 150 from behind the sample cell 105(relative to the second detector 112). If sufficient light sourcesarranged in this way are provided, the highlight lines around the edgeof each particle will form a continuous bright perimeter around eachparticle within the imaging region.

The light beam axis of each dark field light source may be at an angleof less than 60 degrees (or less than 45 degrees) to the imaging axis135. Keeping this angle relatively low means that the reflections fromthe particles received by the second detector are at a relatively lowreflection angle. This in turn means that specular reflections from theparticle surfaces are enhanced, increasing the contrast of the imagedparticles.

As for the light field arrangement of FIG. 1 , the dark field lightsources 102, 103 may be switched off during a light scatteringarrangement, or simultaneous measurement by scattering and imaging maybe used.

In some instruments, both light field and dark field illumination may beprovided, by combining light field and dark field light sources. FIG. 3shows an example of such an instrument, comprising a first light source101, second light source 102, third light source 103 and fourth lightsource 104. A first detector 111 for detecting scattered light andsecond detector 112 for imaging are provided, configured in the same wayas in the examples of FIGS. 1 and 2 . A light trap 160 may be providedbehind the sample cell 105 (from the point of view of the seconddetector 112), along the imaging axis 135.

The first light source 101 is configured in the same way as the firstlight source of FIGS. 1 and 2 , to provide a first light beam 121 forperforming scattering measurements. The second light source 102 isconfigured to provide light field illumination for the second detector112, in the same way is the example of FIG. 1 , but in this embodimentthe second light source 102 may be surrounded by a light trap 160. Thirdand fourth light sources 103, 104 are arranged to provide dark fieldillumination of the sample 150 for imaging by the second detector 112,in the same way as explained with reference to FIG. 2 .

In this arrangement, either dark field light sources 103, 104, or brightfield light source 102 can be used to illuminate the sample 105 forimaging by the second detector 112.

An instrument may be configured to capture sequential bright field andlight field images that are close together in time (for instance withless than 1 s, 0.5 s. 250 ms or 100 s) of separation. The bright fieldand light field image may be correlated or otherwise combined togetherto improve the characterisation of particles by imaging. For example,the bright field image could be inverted and summed with the dark fieldimage. Any particle edges that were missing or of low contrast in oneimage could be supplied by the other image. The maximum tolerable timedelay between bright field and dark field imaging may be determinedbased on a flow rate of the sample 150. If the sample 150 is flowing ata high rate, particles will move a significant distance in a relativeshort time, which may make combining the images more complex.

FIG. 4 shows a further instrument, comprising a first light source 101,second light source 102 and sample cell 105. The first light source 101may be a coherent light source, such as a laser. The second light sourcemay be incoherent, such as an LED. The first light source 101 isconfigured to illuminate a sample 150 within the sample cell 105 using afirst light beam 121 along a first light beam axis, so as to producescattered light 171, 173 by interaction of the first light beam 121 withparticles of the sample 150. The scattered light comprises forwardscattered light 171 and backward scattered light 173. The first lightbeam 121 passes through a first wall of the sample cell 105, thenthrough the sample 150 and then through the second wall of the samplecell 105.

The instrument further comprises a first detector 111 and third detector113, configured to detect the scattered light 171, 173. The firstdetector 111 is arranged to detect forward scattered light 171, and thethird detector 113 is arranged to detect backward scattered light 173.First collection lenses 181a, 181b are provided to collect and focusforward scattered light 171 at the first detector 111, and secondcollection lenses 183a, 183b are provided to collect and focus backwardscattered light 173 at the third detector 113. The first detector 111and third detector 113 are each positioned in different azimuthallocations (with respect to the first light beam axis). In this examplethe first detector 111 and third detector 113 are at an azimuthal offsetof 90°, so that if the first detector 111 receives S polarised scatteredlight, the second detector receives P polarised scattered light. Thismay substantially reduce the amount of optical noise at each of thefirst and third detector 111, 113 by positioning one of these detectoraway from reflections from the other detector.

Each of the collection lenses 181a, 181b, 183a, 183b may comprise anaspheric surface. Each of the collection lenses 181a, 181b, 183a, 183bare sector shaped, when viewed along the first light beam axis, arepositioned with their optical axes coincident with the first light beamaxis, and comprise an open region to allow the first light beam 121 topass by them without contributing to stray light by reflecting from thelenses 181a-b, 183a-b. This open region of each collecting lenssubstantially reduces optical noise, and means that reduced surfacequality (contributing to light scattering) that may be associated withaspheric surfaces is less of an issue, since the first light beam 121does not pass through the aspheric surface. The ability to use asphericsurfaces contributes significantly towards achieving a compact,high-performance scattered light detection arrangement.

The first wall of the sample cell 105 may comprise a convex externalsurface 161 through which the first light beam 121 passes, and thesecond exterior wall of the sample cell 105 may comprise a convexexternal surface 162 through which the first light beam 121 passes. Eachof the first and second wall may comprise a plano-convex lens, eachcomprising a flat internal sample cell surface.

An effect of the curved external surfaces 161, 162 of the sample cellwalls is to allow light scattered at higher angles to escape with lessrefraction at the sample cell air interface. Flat external surfacesresult in spreading out of scattered light as it is refracted at thesample cell wall/air interface, and a critical angle exists at whichscattered light is totally internally reflected. The use of a samplecell 105 with a convex external surface 161 or 162 enables both abroader range of scattering angles to be detected, increases the amountof scattered light per steradian outside the sample cell (becausescattered light is not spread by refraction at the sample cell/aitinterface) and reduces optical noise (because any totally internallyreflected scattered light ends up as optical noise). Furthermore, theconvex external walls 161, 162 decrease deleterious effects of detectinglight from the sample cell 105 at high angles (relative to a normal tothe plane defined by the interior surfaces of the sample cell 105), aswell as increasing the range of angles over which light from the sample150 may be detected. This makes it more straightforward to arrangemultiple detection modalities around the sample cell 105 with differentdetection/imaging axes and different illumination axes (such asscattering detectors 111, 113 and imaging detector 112).

Each of the first detector 111 and third detector 111, 113 may comprisean array of light sensitive elements, each element for detecting lightscattered at a different range of angles. The first detector 111 may beconfigured to detect light scattered at angles of around 20° to around70°. The range of scattering angles detected at the first detector 111may include scattering angles that are higher than the critical anglefor a flat walled cell. The range of scattering angles detected by thefirst detector 111 may be at least 30° (e.g. from 20° to 50°). A furtherdetector (not shown) may be configured to detect lower scatteringangles. The scattered light detected by the further detector may befocussed on the further detector by the second sample cell wall.

The second detector 112 comprises an imaging detector. The plane of animaging lens 182 is schematically illustrated in FIG. 4 , showing howthe sample 150 may be imaged at the second detector 112. The secondlight source 102 is configured to provide bright field illumination ofthe sample 150, and is configured to produce a second light beam 122along a second light beam axis. The second light beam axis issubstantially coincident with the imaging axis of the second detector112, and the second light source 112 thereby provides bright fieldillumination of the sample 150.

In order to provide a high uniformity of illumination, at least one lensmay be provided between the second light source 102 and the sample cell150. In FIG. 4 a collector lens 187 and condenser lens 188 are providedbetween the second light source 102 and the sample cell 105, so as toprovide for a Köhler type optical arrangement in which substantiallyuniform illumination of the first region of the sample cell 105 isprovided.

FIG. 5 shows a further example of scattering instrument, which issimilar to that of FIG. 4 . In FIG. 5 the schematic illustration imaginglens 182 have been replaced with a group of lens elements that togethercomprise the imaging lens 182, and the second detector 112 has beenrepositioned based on the design of the imaging lens 182. The secondlight source 102 and associated optics are the same as described withrespect to FIG. 4 , as is the sample cell 105, first detector 111 andassociated collection lenses 181a, 181b, and the third detector 113 andassociated collection lenses 183a, 183b.

FIG. 5 includes a further detector 111a, for detecting light scatteredfrom the sample 150 at low forward scattering angles (i.e. at a range ofscattering angles that includes angles smaller than the range ofscattering angles received by the first detector 111). Light scatteredby the interaction of the first light beam 121 with the sample 150 isfocussed by the second sample cell wall 162 at the further detector111a. The further detector 111a may be configured to detect lightscattered at angles of less than 1° to angles of at least 10°, forinstance, from 0.1° to 15°.

FIG. 6 illustrates the optical arrangement of the second sample cellwall 142, imaging lens 182 and second detector 112, showing the path ofa first, second and third bundle of rays 191, 192, 193, correspondingwith lower, mid and upper locations within the imaging region of thesample cell 105. This can be compared with a similar illustration for asample cell with flat walls, shown in FIG. 7 .

A further benefit of the second sample cell wall 142 comprising a lensis that the image height, or numerical aperture of the imagingarrangement is increased. In example embodiments, and increase innumerical aperture of around 1.6 is possible.

FIG. 8 illustrates an example imaging optical arrangement which issimilar to that of FIG. 6 , in which a field flattener lens 189 has beenincluded to at least partially compensate for the inclined imaging axiswith respect to the sample cell 105. This may improve image quality atthe second detector 112.

In an alternative arrangement (not shown), the sample cell 105 may be ina different position than shown in FIGS. 4 and 5 . Instead of aligningthe first (scattering) light beam axis with the optical axis of thesample cell 105 (the sample cell optical axis being defined by theoptical axes of the first and second sample cell walls 141, 142), thesample cell optical axis may be aligned (or coincident with) the imagingaxis of the second (imaging) detector 112. This may improve the qualitywith which the sample is imaged by the second detector 112. Thescattering arrangement may be substantially unaffected by this change,due to the reduced refraction at the sample cell/air interfacesresulting from the convex cell surfaces 161, 162.

A number of other variations are possible within the scope of theinvention, which is defined by the appended claims.

The invention claimed is:
 1. A light diffraction particlecharacterisation apparatus comprising: a first light source; a secondlight source, a sample cell; a first detector, comprising a plurality ofdetector elements each corresponding with a different range ofscattering angles; a second detector, different from the first detector;and a processor; wherein: the first light source is operable toilluminate a first region of a sample comprising dispersed particleswithin the sample cell with a first light beam along a first light beamaxis so as to produce scattered light by interactions of the first lightbeam with the sample; the first detector is configured to detect thescattered light; the second light source is operable to illuminate asecond region of the sample with a second light beam along a secondlight beam axis; the second detector is an imaging detector, configuredto image the particles along an imaging axis using the second lightbeam; the first light beam axis is at an angle of at least 5 degrees tothe second light beam axis; and the processor is configured to correlateor cross-reference output from the first detector with output from thesecond detector to perform a light diffraction measurement to derive aparticle size the sample cell comprises a first wall and a second wall,and the first light beam passes through the first wall, then through thesample, then through the second wall, wherein the first and second wallof the sample cell each comprise a convex external surface through whichthe first light beam axis and the second light beam axis passes.
 2. Theparticle characterisation apparatus of claim 1, wherein the sample cellcomprises a first wall and a second wall, and the first light beampasses through the first wall, then through the sample, then through thesecond wall, wherein the first and second wall of the sample cell eachcomprise a convex external surface through which the first light beamaxis and the second light beam axis passes.
 3. The particlecharacterisation apparatus of claim 2 1, wherein the first and secondwall each comprise a plano-convex lens defined by the respective convexexternal surface, the optical axes of the first and second wall defininga sample cell optical axis.
 4. The particle characterisation apparatusof claim 3, wherein the second light beam axis is at an angle of atleast 10° to the sample cell optical axis.
 5. The particlecharacterisation apparatus of claim 1, wherein the first light source,sample cell and first detector define a scattering plane, and the secondlight source and second detector are disposed offset from the scatteringplane, occupying a different azimuthal orientation about the first lightbeam axis.
 6. The particle characterisation apparatus of claim 1,comprising a collecting lens between the sample cell and the firstdetector, wherein the collecting lens comprises an aspheric surface. 7.The particle characterisation apparatus of claim 6, wherein thecollecting lens comprises an optical axis that is coincident with thefirst light beam axis.
 8. The particle characterisation apparatus ofclaim 1, comprising a processor, wherein the processor is configured tocorrect a size of an imaged particle based on a location of the particleimage at the second detector.
 9. The particle characterisation apparatusof claim 1, comprising a condenser lens between the second light sourceand the sample cell and a collector lens between the condenser lens andthe second light source, wherein the second light source, collector lensand condenser lens are arranged to provide Köhler illumination of aregion within the sample cell.
 10. The particle characterisationapparatus of claim 1, wherein the second detector is arranged on a pathof the second light beam, so as to perform light field imaging ofparticles within the sample cell.
 11. The particle characterisationapparatus of any claim 1, wherein the second detector is arranged offthe a path of the second light beam, so as to perform dark field imagingof particles within the sample cell.
 12. The particle characterisationapparatus of claim 10, comprising a third light source arranged toprovide a third light beam that is not directly received by the seconddetector, so that the apparatus is configured to perform dark fieldimaging when the sample is illuminated by the third light source and notby the second light source.
 13. The particle characterisation apparatusof claim 1, wherein the first region is at least partly coincident withthe second region.
 14. The particle characterisation apparatus of claim1, wherein the second detector is configured to image the sample alongan imaging axis, and the imaging axis is at an angle of at least 5degrees to the first light beam axis.